Infection of the genital tract by human papillomaviruses (HPVs) represents the most common sexually transmitted disease, resulting in squamous intraepithelial lesions (SIL) that can progress to cancer. Our overall goal is to understand the natural history of genital HPVs in order to prevent infection or progression to neoplasia. The development of serological assays has greatly accelerated our understanding of the natural history, and the characterization of antibody responses forms the underpinnings of vaccine strategies. Our previous collaborative studies have found that the majority of HPV infected women develop type-specific serum IgG antibodies directed against conformational epitopes present on the LI capsid protein. The current application proposes to characterize the serum antibody response in more detail, in both women and men. The specific aims are: 1) To identify the immunoreactive epitopes on HPVs 6 and 16 LI recognized by sera from women who develop antibody responses following infection, and determine whether there is a detectable maturation of the antibody response over time. 2) To identify the risk factors associated with serum IgG antibodies in men since most of our understandingof the natural history of HPV capsid antibodies is based largely on cohorts of women with incident infection. 3) To determine why a substantial fraction, approximately 15-30%, of women with HPV DNA in the genital tract fail to seroconvert. 4) To characterize the mucosal antibody response. And, 5) To examine the hypothesis that antibody correlates with protection from re-infection.